Figure - available via license: Creative Commons Attribution 4.0 International
Content may be subject to copyright.
(A) Western blotting of maspin and housekeeping protein β-actin in the total lysates of parental KYSE510, M-KYSE510, and V-KYSE510 cells. (B) MTT assay of the proliferation of parental KYSE510, M-KYSE510, and V-KYSE510 cells, cultured in the maintenance media. (C) Representative staining of single cell-derived colonies (bottom) and the magnified image of the highlighted colonies (top) from the colony formation assay. (D) Quantification of colonies with more than >100 cells/colony based on counting under microscope in the colony formation assay. Data represent the average of three independent repeats. Error bars represent the standard deviation. The difference between M-KYSE51 and V-KYSE510 (or parental KYSE510) was statistically significant (p<0.001).
Source publication
Tumor suppressor maspin is a differentially regulated gene in the progression of many types of cancer. While the biological function of maspin in blocking tumor invasion and metastasis is consistent with the loss of maspin expression at the late stage of tumor progression, the differential expression and the biological significance of maspin in ear...
Similar publications
Objective: Overexpression of METCAM/MUC18, an immunoglobulin-like cell-adhesion molecule, promotes tumorigenesis and progression of human breast cancer cells. We also observed an intriguing phenomenon that a high-expressing SK-BR-3 clone manifested a transient tumor suppression effect in vivo. The purpose of this study was to understand if this was...
The aim of the present study was to examine microRNA (miRNA or miR)-455-5p expression in esophageal squamous cell carcinoma (ESCC) at the tissue and cellular levels in order to elucidate its biological roles. A total of 60 patients with ESCC were enrolled in the present study and reverse transcription-quantitative polymerase chain reaction was used...
Citations
... At the same time, maspin protein is lowly expressed in endometrial cancer with high pathological staging and poor differentiation, and vice versa (51). According to research, overexpression of maspin is associated with better overall survival in esophageal and oral squamous cell carcinoma (52,53). Zheng et al (50) found that SERPINB5 mRNA expression is positively associated with overall survival and progression-free survival in patients with gastric cancer, and even after stratification based on clinical and pathological characteristics. ...
Maspin is a serine protease inhibitor that is encoded by the human SERPINB5 gene. As a tumor inhibitor, it can inhibit the growth of tumor cells, increase adhesion between tumor cells and inhibit tumor angiogenesis. In the present study, a meta- and bioinformatics analysis was performed through the PubMed and China National Knowledge Infrastructure databases including entries added until up to March 20, 2023. It was found that compared with normal breast tissue, maspin expression was downregulated in breast cancer tissue. Maspin expression was negatively associated with lymph node metastasis. According to Kaplan-Meier plotter, it was found that lower maspin expression was negatively associated with the overall and distant metastasis-free survival rate of patients with estrogen receptor-positive, luminal A and grade 2 breast cancer. High expression of maspin was also positively associated with the relapse-free survival rate of patients of the luminal A subtype. Low maspin expression was positively associated with the post-progression and distant metastasis-free survival rate of the progesterone receptor-negative subtype. According to the GEPIA database, SERPINB5 mRNA expression was higher in normal than breast cancer tissues and negatively correlated with the TNM stage. High expression of maspin was also positively associated with the overall survival rate. In the UALCAN database, it was found that the mRNA and promoter methylation levels of SERPINB5 were higher in normal than in breast cancer tissues. These findings suggest that the expression of maspin may serve as a potential marker to indicate the occurrence, subsequent progression and even prognosis of breast cancer.
... The association between MASP expression and better overall survival in ESCC was studied by Wang et al. The authors revealed that cancer patients who showed low or moderate MASP expression had lower postoperative survival rates than those who showed high MASP expression [73]. This leads to the conclusion that the transient regulation of MASP in the early stage of ESCC development may be a kind of defence mechanism, which prevents further progression to more malignant phenotypes, ultimately inhibiting tumour progression. ...
Gastrointestinal (GI) cancers, which are a diverse group of malignant diseases, represent a major healthcare problem around the world. Due to the lack of specific symptoms in the early stages as well as insufficient diagnostic possibilities, these malignancies occupy the leading position in the causes of death worldwide. The currently available tests have too many limitations to be part of routine diagnostics. Therefore, new potential biomarkers that could be used as diagnostic and prognostic factors for these cancers are still being sought. Among the proteins that might fit this role are serpins, which are serine protease inhibitors. Although the serpins themselves have been known for many years, they have recently become the centre of attention for many authors, especially due to the fact that a number of proteins in this family are involved in many stages of neoplasia formation, from angiogenesis through tumour growth to progression. Therefore, the aim of this review is to present the current knowledge about the significance of serpins in GI malignancies, especially their involvement in the development and progression of oesophageal, gastric, pancreatic and colorectal cancers. This review summarises and confirms the important roles of selected serpins in the pathogenesis of various GI cancers and also points to their promising roles as therapeutic targets. However, due to the relatively nonspecific nature of serpins, future research should be carried out to elucidate the mechanisms involved in tumour pathogenesis in more detail.
... Maspin is a member of the serine protease inhibitor/ non-inhibitor superfamily (serpin) being expressed in epithelia especially in the nucleus of normal cells [48,49]. It has been shown that downregulation or translocation of Maspin from the nucleus to the cytoplasm correlated with a poor prognosis and a low survival of cancer patients [50][51][52]. These being explained by the fact that Maspin is a proteases inhibitor which prevents metastasis and tumor progression controlling apoptosis of tumor cells and also the tumor angiogenesis [53,54]. ...
Squamous cell carcinoma (SCC) is the most frequent cancer in oral cavity and its prognosis has exhibited little improvement in the last decades. Although much less common palate SCCs manifests a higher local aggression invading very quickly the adjacent muscles and jawbones, thus being able frequently to lead to dysfunctions in chewing, swallowing, and speech. To elucidate what underlies such local aggression, we investigated the immunohistochemical expression in palate SCCs of Podoplanin (D2-40), Galectin-3 (Gal-3), mammary serine protease inhibitor (Maspin) and minichromosome maintenance complex component 7 (MCM7), markers that are known to be involved in tumor invasiveness. We found a progressive increase in reactivity for D2-40 and MCM7 from the normal epithelium toward dysplastic epithelium and respectively to SCC, which suggests the intervention of these markers in the early stages of squamous cell carcinogenesis in the palate. The highest D2-40, Gal-3 and MCM7 reactivity was observed in basaloid and in poorly differentiated (G3) palate SCCs, while for Maspin the well-differentiated (G1) palate SCCs were the most reactive. The first three markers mentioned above were most intensely expressed at the invasion front, while the Maspin reactivity was low or absent at this level. Statistically, we found significant stratification on localization, grading, muscle invasion, and survival for all investigated markers, but with very high direct correlations between D2-40, Gal-3, and MCM7 immunoreactive score (IRS) values, while between the Maspin and each of the previous markers there were very high inverse correlations. Overall, all these investigate markers proved to be responsible for the local invasiveness and regional lymph node metastasis, thus allowing a prognostic and therapeutic stratification of patients with palate SCCs.
... [20][21][22] Higher SERPINB5 expression has been also reported to be associated with better prognosis for non-small cell lung cancer, esophageal squamous cell carcinoma, ovarian cancer and bladder cancer. [23][24][25][26] In this study, SERPINB5 expression was increased in LUSC tissues compared to adjacent normal. SERPINB5, as one of hub proteins, was signi cantly enriched in p53 signaling pathway. ...
Background: This study aimed to find biomarkers with diagnostic and prognostic for lung squamous cell carcinoma and to validate key biomarkers in vitro
Methods：RNA sequencing was used to identify differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs) between LUSC and normal tissue. Using published dataset, we also validated the result of RNA sequencing. The diagnostic and prognostic value of candidate genes were evaluated by ROC curve analysis and survival analysis, respectively. To uncover the confirm effect of MIR205HG in LUSC, we knocked down MIR205HG expression in NCI-H520 cells. Then, MTT assay and transwell assay was used to detect the effect of MIR205HG on cell proliferation and migration.
Rsults: In total, 1946 DEmRNAs and 428 DElncRNAs were identified in LUSC compared to normal tissues. A total of 147 DElncRNAs-nearby target DEmRNAs pairs and 851 DElncRNA-DEmRNA co-expression pairs were obtained. Except for NEAT1, expression of the others in the The Cancer Genome Atlas (TCGA) results was consistent with our RNA sequencing, generally. ROC curve analysis displayed that the MCM2, SERPINB5, ITGB8, CASC19 and MIR205HG could predict the occurrence of LUSC. Survival analysis suggested that SERPINB5, NEAT1 and MIR205HG had potential prognostic value for LUSC. Knockdown of MIR205HG inhibits cell proliferation and migration in NCI-H520 cell. In addition, knockdown of MIR205HG significantly reduced the expression of ITGB8.
Conclusions: This data may contribute to uncover the pathogenesis of LUSC and provide new and accurate therapeutic targets for LUSC.
... MCM2 belongs to the MCM family and has been identified as a biomarker for the progression and prognosis of several types of human cancers (24). MCM2 is highly expressed in a variety of human cancers, including breast cancer, stomach cancer, colorectal cancer, lung cancer, and hepatocellular carcinoma (25)(26)(27)(28)(29)(30)(31). Wu et al. reported that the expression level of MCM2 was upregulated in LUSC tissues and cell lines, and that MCM2 was related to the low overall survival of LUSC patients (32). ...
... SERPINB5, a member of the serpin superfamily, is a serine protease inhibitor that suppresses tumor progression and metastasis (33)(34)(35). Higher SERPINB5 expressions have been reported to be associated with better prognosis in non-small cell lung cancer, esophageal squamous cell carcinoma, ovarian cancer, and bladder cancer (25)(26)(27)36). In the present study, SERPINB5 expression was increased in LUSC tissues compared with normal tissues. ...
Background:
The aim of the present study was to find diagnostic and prognostic biomarkers for lung squamous cell carcinoma (LUSC) and to validate key biomarkers in vitro.
Methods:
RNA sequencing was used to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed long non-coding RNAs (DElncRNAs) in LUSC tissues. RNA sequencing results were validated using a published dataset. Diagnostic and prognostic values of candidate genes were evaluated by receiver-operating characteristic (ROC) curve analysis and survival analysis, respectively. To determine the effect of MIR205HG in LUSC, MIR205HG expression was knocked down in NCI-H520 cells. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Transwell assay were used to respectively detect the effect of MIR205HG on cell proliferation and migration.
Results:
In total, 1,946 DEmRNAs and 428 DElncRNAs were identified in LUSC compared with normal tissues. A total of 851 DElncRNA-DEmRNA co-expression pairs were obtained. With the exception of NEAT1, MCM2, SERPINB5, ITGB8, CASC19, and MIR205HG were upregulated in LUSC. ROC curve analysis indicated that MCM2, SERPINB5, ITGB8, CASC19, and MIR205HG could predict LUSC. Survival analysis suggested that SERPINB5, NEAT1, and MIR205HG had potential prognostic value for LUSC. MIR205HG knockdown inhibited cell proliferation and migration, and significantly reduced the expression of ITGB8.
Conclusions:
The findings of the present study could help determine the pathogenesis of LUSC and provide new and accurate therapeutic targets for its treatment.
... Maspin is a protein implicated in the regulation of actin cytoskeleton leading to a less invasive phenotype and a lower metastatic spread. In esophageal SCC, lower immunoreactivity for maspin has been associated with worse prognosis (7). However, the effect on prognosis differs depending on its localization, with the nuclear Maspin acting as a suppressor of metastasis (16) while cytoplasmic expression is associated with more aggressive tumors (17). ...
Background/aim:
In metastatic head and neck squamous cell carcinoma (HNSCC) the metastatic tumor does not always keep the same gene expression profile as the parental tumor, which may influence the course of the disease. The aim of this study was to compare the expression of genes implicated in HNSCC carcinogenesis between the primary tumor and the corresponding lymph node metastasis.
Materials and methods:
Eighteen HNSCC, their corresponding node metastases and non-neoplastic tissues were studied by RT-qPCR for the expression of EGFR, VEGF, claudin7, maspin, survivin and SCCA. The levels of expression were correlated with histological characteristics and patients' prognosis.
Results:
All genes except for survivin displayed different expression in node metastasis compared to the primary tumor. The expression of EGFR, survivin, maspin, and claudin7 in node metastasis and SSCA in the primary tumor affected the prognosis. SCCA expression is associated with the expression of claudin7 and maspin. P16-positive tumors expressed low levels of VEGF and SCCA, while keratinizing tumors over-expressed VEGF.
Conclusion:
Differential gene expression levels in node metastases compared to the primary tumor is linked to the prognosis of HNSCC patients. The histological/immunohisto-chemical characteristics of the tumor are associated with these genes expression changes.
... Esophagus: Maspin can show infrequent cytoplasmic positivity in squamous cell epithelium [53][54][55] (Table 2). In SCC cells, downregulation of maspin was noted compared with the adjacent normal epithelium. ...
... In SCC cells, downregulation of maspin was noted compared with the adjacent normal epithelium. Strong nuclear staining is associated with favorable prognosis, increased patient survival, and a lower pTN stage while high cytoplasmic staining correlates with the presence of lymph node metastases [53,54] . Based on an in vitro study, which used esophageal SCC cell lines, it was hypothesized that the inhibitory effect of maspin is based on switching the metabolic phenotype to low glycolysis through disrupting the hypoxia inducible factor 1α [55] . ...
... [16][17][18][19][20] Higher MASPIN expression has been also been found to be associated with better prognosis for breast 8 pros- trate, colon, oral, squamous cancers 9 and esophageal squamous cell carcinoma. 21 However, it always not hold true. MASPIN overexpres- sion was observed in pancreatic 10 and ovarian cancer, 22 whereas nor- mal control tissue was MASPIN negative. ...
... Maspin is a secretory protein [4] that has been 1 3 shown to restrict tumor progression by inhibiting tumor proliferation, invasion, metastasis, motility, and inducing tumor cell apoptosis [4][5][6][7]. Investigation of clinic data reveals that the down-regulation of maspin is correlated with worse diagnosis and poorer overall survival of cancer patients [8][9][10]. More importantly, Zhanget al. [11] found that both recombinant and secreted maspin could block vascular endothelial growth factor (VEGF)/basic fibroblast growth factor (bFGF)-induced migration of vascular endothelial cells in a dose-dependent manner, indicating that maspin possesses an anti-angiogenesis activity. ...
Maspin is known as a tumor suppressor and a potent angiogenesis inhibitor, however, its effects on proliferative diabetic retinopathy (PDR) have not been fully elucidated. This study aimed at evaluating the effects of maspin on high glucose-induced oxidative stress and angiogenesis in human retinal microvascular endothelial cells (HRMECs). Herein, HRMECs were treated with 0.25, 0.5, or 1 µM recombinant human maspin in the presence of 30 mM glucose, and their proliferation, tube formation, and oxidative stress responses were further detected. Our results revealed that maspin inhibited the high glucose-induced proliferation, migration, and tube formation of HRMECs. Maspin also decreased reactive oxygen species, nitric oxide level, and increased glutathione S-transferase activity in HRMECs. Meanwhile, maspin reduced the mRNA and protein levels of hypoxia-inducible factor-1α and vascular endothelial growth factor in high glucose-stimulated cells in a dose-dependent manner. Additionally, the high glucose-induced elevation of phosphorylated phosphoinositide-3-kinase (p-PI3K) and phosphorylated AKT was also suppressed by maspin. In summary, our data suggest that maspin inhibits high glucose-induced proliferation, oxidative stress, and angiogenesis of HRMECs at least by modulating the PI3K/AKT pathway. Maspin may be a potential therapeutic agent for the prevention and treatment of PDR.
... According to a report by the Esophageal Cancer Collaboration, the depth of tumor invasion, regional lymph node metastasis and distant metastasis are associated with decreased patient survival time (1). Although early EC diagnosis and treatment are improving, the prognosis for EC with extensive invasion and metastasis remains poor (2,3). ...
Galectin-3 is a multifunctional β-galactoside binding lectin associated with tumor progression. Previous studies confirmed the roles of galecin-3 overexpression and silencing in the biological behavior of Eca109 human esophageal cancer (EC) cells; galectin-3 may serve a critical role in the vasculogenic mimicry (VM) of tumors. Therefore, the present study examined the effects of galectin-3 knockdown using lentivirus vectors on VM in EC. Eca109 and EC9706 EC cells were transfected with a lentiviral vector to inhibit galectin-3 expression, or a control vector. VM formation in vitro was evaluated via 3D culture. Western blotting was used to detect the expression level of galectin-3 following galectin-3 silencing and the expression levels of VE-cadherin, ephrin type-A receptor 2 precursor (EphA2) and matrix metalloproteinase 2 (MMP-2). According to the results of western blot analysis, the Eca109/galectin-3 and EC9706/galectin-3 cells exhibited effective galectin-3 silencing (P<0.05). Eca109 and EC9706 cells formed typical tubular networks; the number of tubular networks markedly decreased subsequent to galectin-3 knockdown. The expression levels of MMP-2 and EphA2 proteins in Eca109/galectin-3 and EC9706/galectin-3 cells were lower compared with those in Eca109, EC9706, and control vector-transfected Eca109 and EC9706 cells (P<0.05); however, there was no significant difference in the expression of VE-cadherin proteins. These results indicated that galectin-3 may modulate VM in EC by regulating the EphA2 expression level, which affects VM formation via MMP-2.
